The present invention relates to the field of chemical synthesis and manufacturing, and more particularly, to a continuous process of preparing bromopicrin, and highly pure bromopicrin produced therefrom.
Bromopicrin (CAS Registry No. 464-10-8), synonymously known as 1,1,1-tribromonitromethane (methane, tribromonitro-), nitrotribromomethane (methane, nitrotribromo-), and nitrobromoform, has a chemical formula of CBr3NO2, a molecular weight of 297.728 grams/mol, a melting point of 10° C., a boiling point of 89-90° C. (at 20 mm Hg), a specific gravity of 2.79, water solubility of about 1.5 grams per liter water (at 20° C.), and appears either as prismatic crystals in the solid phase, or as an oily colorless liquid.
Bromopicrin belongs to the general chemical family of halonitroalkanes (or equivalently, nitrohaloalkanes), which includes, for example, mono-, di-, and tri-, bromonitroalkanes and mono-, di-, and tri-, chloronitroalkanes, such as mono-, di-, and tri-, bromonitromethanes and mono-, di-, and tri-, chloronitromethanes, respectively.
Selected examples of bromonitromethanes, such as bromopicrin, and uses thereof, are disclosed in U.S. Pat. No. 5,866,511, to Dallmier, et al.; U.S. Pat. No. 5,591,759, to Ito, et al., U.S. Pat. Nos. 5,411,990, and 5,397,804, each to Tsuji, et al.; U.S. Pat. No. 5,013,762, to Smith, et al.; and U.S. Pat. Nos. 4,039,731; 4,020,249; 4,017,666; and 3,968,096, each to Freedman, et al.
WO 2006/061842, by the present assignee, teaches novel pesticide formulations of bromopicrin and methods of using same for disinfecting substances, products or structures and particularly for controlling plant pests.
It is worthy to note that in none of these disclosures was there any mention of the purity or source of the bromonitromethane, in particular of bromopicrin, let alone an indication of the synthesis or manufacturing of the bromonitromethane.
Selected examples of bromopicrin used as a consumable reactant or ingredient in processes of preparing another composition or formulation are provided in the disclosures of U.S. Pat. Nos. 5,219,938, 5,128,416, 5,015,692, and 4,957,976, but none of these disclosures describes a process of preparing bromopicrin, nor of its purity level. In U.S. Pat. No. 4,922,030, another bromonitromethane, monobromonitromethane, is custom synthesized for the subsequent preparation of monobromonitroalcohol.
In general, methods or processes of synthesizing and/or manufacturing halonitroalkanes are well known and described, for example, in Tscherniak, in Ann. 180, 128-130 (1876); U.S. Pat. No. 2,309,806, to Tindall; U.S. Pat. No. 2,633,776, to Slagh; U.S. Pat. No. 4,922,030, to Nocito, et al.; U.S. Pat. No. 5,043,489, to Nocito, et al.; and U.S. Pat. No. 5,180,859, to Timberlake, et al.
Since bromopicrin is a halonitroalkane, one might expect that these processes will be applicable in the preparation of bromopicrin. However, it turns out that bromopicrin and dibromonitromethane are only described therein in the context of undesirable polyhalogenated nitromethane low-yield by-products or impurities of the desired monobromonitromethane product. Hence, in none of the above disclosures is there a description of a method of preparing pure bromopicrin as the target product in high yield.
Preparation of Bromopicrin by the Distillation of an Aqueous Mixture of Picric Acid, calcium hydroxide, and bromine, was first disclosed by Stenhouse, in Annalen 91, 307 (1854). It is also known that bromopicrin can be prepared by a reaction of picric acid with a basic metal hypobromite, wherein the bromopicrin product is isolated in high yield by distillation.
These processes suffer several significant disadvantages and limitations, as follows:
a) picric acid is potentially explosive under even mild conditions, and therefore, using picric acid as a reactant involves working at potentially hazardous conditions.
b) bromopicrin is a highly energetic compound, having a relatively high exothermic heat of decomposition (HOD), whereby about 1700 Joules/gram are released during its decomposition. Thus, bromopicrin is potentially hazardous under certain conditions, for example during its recovery and purification from the reaction mixture by distillation.
c) even when using solvent extraction instead of distillation for recovering and purifying bromopicrin from the reaction product, then an extraction procedure needs to be incorporated into the overall method, thereby introducing an organic solvent into an otherwise organic solvent-free method, which would add additional costs, health hazards, and organic solvent waste management, to the overall method.
d) this process is inapplicable as a large volume industrial sized process, due to the high cost of scaling up the bromopicrin recovery and purification stages.
WO 2007/023496, by the present assignee, filed Aug. 22, 2006, discloses for the first time a novel batch process for the preparation of bromopicrin which does not use picric acid as a starting material, thus overcoming the above detailed drawbacks. The process taught in WO 2007/023496 is based on a reaction of bromine, nitromethane (NM) and an alkaline substance, as depicted by the following ‘generalized’ chemical equation (aq.=aqueous):Nitromethane+bromine+alkaline substance (aq.)→bromopicrin+H2O+secondary products (organic phase) (aqueous phase)
In an exemplary preferred embodiment of this process, the alkaline substance is a metal alkali base, such as sodium hydroxide or potassium hydroxide.
As taught in WO 2007/023496 the process is effected by first obtaining a mixture of nitromethane and bromine, preferably in the presence of water and without adding any organic solvent. Then, the alkaline substance is added in portions to the mixture and rapidly and selectively reacts with the bromine contained in the nitromethane mixture, and forms one or more bromine-containing chemical intermediate(s), which in turn, selectively react(s) with the already present nitromethane, thus selectively forming the desired high purity bromopicrin product in high yield. Once the reaction is completed, the heavier (lower) organic phase, containing the bromopicrin, is separated from the lighter (upper) aqueous phase, and bromopicrin is thus collected from the reaction mixture.
According to the teachings of WO 2007/023496 the recommended reaction conditions for the preparation of bromopicrin were determined to be:
Temperature in the reactor: 40° C. (±5)
Br2/Nitromethane molar ratio: 3.25 (±0.03)
Concentration of aqueous NaOH: 35% by weight (±1)
Reaction time (time of addition of base): 4-6 hours
Under these conditions, the selectivity of the reaction is more than 96%, even more than 99%, and the yield is high: e.g., between 92% and 94.5% (based on nitromethane). The selectivity and yield of the process depend on the temperature of the reaction (TR), the molar ratio between the bromine and the nitromethane and the time period during which the base is added. In this respect, it was determined that the formation of the impurities could be prevented by using a sufficiently high starting Br2:nitromethane molar ratio (for example, about 3.25).
Thus, the process disclosed in WO 2007/023496, overcomes the disadvantages of previously-known methods for the preparation of bromopicrin from picric acid, while obtaining a high yield and high quality bromopicrin product.
As known in the design of industrial chemical processes, process reactors are defined as either batch or continuous processors, based upon the mode in which they handle samples or product for processing. Batch process reactors are the simplest mode of reactor operation. In this mode, the process reactor is loaded with medium and the reaction is allowed to proceed. When the reaction is completed, the contents are emptied for downstream processing. The reactor is then cleaned, re-filled, re-inoculated and the reaction process starts again.
In continuous process reactors, fresh media is continuously added and reactor fluid (containing waste as well as desired products) is continuously removed. The reactor can thus be operated for long periods of time without having to be shut down. Continuous process reactors can be many times more productive than batch reactors and are generally the preferred mode in industrial processing, being more time- and cost-effective.
To date, no continuous process has been described for the preparation of bromopicrin from nitromethane and bromine, in the presence of a base.